DESCRIPTION: The principal goal of this research is to develop new techniques and procedures of value to practitioners of biomedical analysis that are based on the special and emerging capabilities of time-of-flight mass spectrometry (TOFMS), especially in conjunction with electrospray ionization (ESI). The special qualities made possible by recent developments in TOFMS are the generation of over 50 mass spectra per second and the achievement of nearly 100 percent sample utilization efficiency leading to sensitivities that potentially exceed that of mass spectrometers monitoring only a few mass values. The implications for chromatographic detection include significantly lower detection limits and (through the additional data of the full spectrum) an increase in analytical resolving power (discrimination against interference) of at least 10 fold. A system for rapid and sensitive screening of bodily fluids for drugs of abuse will be developed using these capabilities along with fast liquid chromatography and electrospray ionization. In addition, a system for the optimization of conditions for the ESI of particular compounds will be developed based on a predictive model just developed in this laboratory. Finally, a tandem TOFMS instrument using both laser photodissociation and laser-assisted collision-induced dissociation will be used in a collaborative biomedical study aimed at determining the sites of post-translational acylation and the rate of fatty acid turnover in proteolipid protein. It will also be used to study the singly and multiply-charged ions formed by ESI by means of their fragmentation mass spectra relating these also to the ESI model.